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【结 构 式】 
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【分子编号】40398 【品名】3-methyl-5-(4-piperidinylmethoxy)phenyl 2-chlorobenzenesulfonate 【CA登记号】 |
【 分 子 式 】C19H22ClNO4S 【 分 子 量 】395.90672 【元素组成】C 57.64% H 5.6% Cl 8.95% N 3.54% O 16.16% S 8.1% |
合成路线1
该中间体在本合成路线中的序号：(VI)The monosulfonation of orcinol (I) with 2-chlorobenzenesulfonyl chloride (II) in ethyl ether/aqueous NaHCO3 gives the monosulfonate (III), which is condensed with 4-(methanesulfonyloxymethyl)piperidine-1-carboxylic acid tert-butyl ester (IV) by means of NaH in DMF to yield the aryl ether (V). The deprotection of (V) with 4N HCl in dioxane affords the piperidine (VI), which is finally treated with amidinosulfonic acid (VII) and TEA in DMF. The 4-(methanesulfonyloxymethyl)piperidine-1-carboxylic acid tert-butyl ester (IV) has been obtained as follows: The reaction of piperidine-4-carboxylic acid (VIII) with Boc2O and NaHCO3 in dioxane/water gives the protected piperidine (IX), which is reduced at the carboxyl group by means of BH3/THF yielding the carbinol (X). Finally, this compound is mesylated with MsCl and TEA in dichloromethane to afford the target intermediate.
| 【1】 Soll, R.M.; Spurlino, J.; Murphy, L.; Lu, T.; Salemme, F.R.; Bone, R.; Illig, C.R.; Tomczuk, B.E.; Structure-activity and crystallographic analysis of a new class of non-amide-based thrombin inhibitor. Bioorg Med Chem Lett 2000, 10, 1, 79. |
| 【2】 Zetter, B.R.; Smith, R. (Children's Medical Center Corp.); Treatment of human prostate cancer with spermine. WO 9711691 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 27257 | 5-Methyl-1,3-benzenediol; Orcinol | 505-15-4 | C7H8O2 | 详情 | 详情 |
| (II) | 30817 | 2-chlorobenzenesulfonyl chloride | 2905-23-9 | C6H4Cl2O2S | 详情 | 详情 |
| (III) | 30818 | 3-hydroxy-5-methylphenyl 2-chlorobenzenesulfonate | C13H11ClO4S | 详情 | 详情 | |
| (IV) | 40396 | tert-butyl 4-([[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]methyl)-1-piperidinecarboxylate | C14H27NO3S | 详情 | 详情 | |
| (V) | 40397 | tert-butyl 4-[(3-[[(2-chlorophenyl)sulfonyl]oxy]-5-methylphenoxy)methyl]-1-piperidinecarboxylate | C24H30ClNO6S | 详情 | 详情 | |
| (VI) | 40398 | 3-methyl-5-(4-piperidinylmethoxy)phenyl 2-chlorobenzenesulfonate | C19H22ClNO4S | 详情 | 详情 | |
| (VII) | 15984 | amino(imino)methanesulfonic acid | CH4N2O3S | 详情 | 详情 | |
| (VIII) | 17402 | 4-nipecotic acid;piperidine-4-carboxylic acid;p-nipecotic acid; Isonipecotic acid; Hexahydroisonicotinic acid; 4-Piperidinecarboxylic acid | 498-94-2 | C6H11NO2 | 详情 | 详情 |
| (IX) | 17404 | 1-(tert-butoxycarbonyl)-4-piperidinecarboxylic acid; 1-BOC-piperidine-4-carboxylic acid; N-Boc-isonipecotic acid | 84358-13-4 | C11H19NO4 | 详情 | 详情 |
| (X) | 40399 | tert-butyl 4-(hydroxymethyl)-1-piperidinecarboxylate | C11H21NO3 | 详情 | 详情 |